Attenuation of anticonvulsant effects of diazepam after chronic treatment with bicuculline

Changes in the GABAergic system after chronic treatment with bicuculline were examined in two strains of inbred rats, Fischer 344 (F344) and Lewis (LEW). Rats received an IP injection of either bicuculline (2 mg/kg) or vehicle once a day for 12 days. After this chronic treatment, the effects of diazepam (1 mg/kg, IP) and pentobarbital (20 mg/kg, IP) on bicuculline-induced convulsions were measured. Bicuculline was acutely infused into a tail vein at 0.0415 mg/min, and the infusion was terminated when rats showed seizure. Following the chronic bicuculline treatment, the anticonvulsant effect of diazepam, but not of pentobarbital, was significantly reduced as compared to its effect following chronic vehicle treatment in both strains. Both diazepam and pentobarbital showed a significant difference in anticonvulsant effects between strains (F344 > LEW). The hypnotic effects of muscimol, barbital, pentobarbital, and ethanol following chronic bicuculline treatment were examined. There was no significant difference in sleep time induced by these drugs between bicuculline- and vehicle-treated rats. These results suggest that the attenuation of diazepam's anticonvulsant effect after chronic bicuculline treatment may result from functional changes in benzodiazepine receptors and that the anticonvulsant effects of diazepam and pentobarbital may be influenced by genetic factors. Moreover, the hypnotic effects of several drugs tested are apparently not affected by chronic bicuculline treatment.     

Pulmonary vascular disease and operative indications in complete atrioventricular canal defect in early infancy

Pulmonary vascular disease was morphometrically analyzed in 67 patients (mean age, 19 months) with isolated complete atrioventricular canal defect. Complete obstruction of the small pulmonary arterial lumen resulting from acute fibrous proliferation and atrophy of the peripheral arterial media, which were considered absolute operative contraindications, were characteristic in six patients with Down's syndrome. Morphometric analysis of medial thickness revealed that thinning of the media of the small pulmonary arteries is generally observed at around 6 months of age in patients with complete atrioventricular canal defect and that the media in patients who have complete atrioventricular canal defect and Down's syndrome was thinner than that in such patients without Down's syndrome. These results suggest that thinning of the media as a result of two factors--Down's syndrome and aging--facilitates the rapid occurrence of fibrous intimal proliferation. Therefore intracardiac repair is desirable within 6 months of life, before medial thinning, in patients with complete atrioventricular canal defect and Down's syndrome. Excluding patients with absolute operative contraindications, the scores of the index of pulmonary vascular disease in operative survivors were below 2.0 and death occurred when scores were more than 2.2. The pulmonary vascular resistances measured in room air and by the oxygen inhalation and tolazoline tests in patients with operative contraindications were more than 7.3, 3.8, and 6.6 units.m2, respectively. We thus conclude that lung biopsy should be undertaken for patients in whom pulmonary vascular resistance is beyond these values to determine the appropriateness of surgical intervention.     

Review of the maximum efficiency of transmission lines

The problem of maximum efficiency of power transmission lines, solved earlier by the author, is reviewed, clarified, and completed through a detailed analysis of the mathematical properties and physical characteristics involved. The results are presented in a form useful to teachers, students, and practicing engineers in electrical power     

Competitive inhibition by procaine of carbachol-induced stimulus-secretion coupling in rat pancreatic acini

1. Procaine (0.03-10 mM) inhibited carbachol (CCh)-induced amylase release from rat isolated pancreatic acini in a competitive manner. Kinetic analysis of the relation between CCh concentrations and the amount of amylase released in the presence of various procaine concentrations indicated that procaine caused competitive inhibition with the affinity constant (pA2) value of 5.00 +/- 0.08. 2. Receptor binding assay confirmed that procaine (0.01-10 mM) competitively inhibited [N-methyl-3H]-scopolamine chloride ([3H]-NMS) binding to its receptor with binding affinity (pKi) of 4.63 +/- 0.10. 3. Procaine transformed CCh-evoked [Ca2+]i dynamics: the initial rise in [Ca2+]i followed by a gradual decay during continuous stimulation with 3 microM CCh was transformed by 0.3 mM procaine to the oscillatory [Ca2+]i dynamics, which resembled the response to 0.3 microM CCh in the absence of procaine. The initial phase of [Ca2+]i oscillation corresponded to the initial phase of CCh-induced amylase release in isolated perfused acini. 4. Procaine (0.3-3 mM) did not inhibit the secretory response to cholecystokinin octapeptide (CCK-8) in isolated incubated acini. A higher concentration of procaine (10 mM) caused weak but significant inhibition of the response to only limited concentrations of CCK-8, 30 and 100 pM. Procaine lower than 10 mM was ineffective on [125I]-BH-CCK-8 binding, although procaine (10 mM) caused weak but significant inhibition of the binding.     

A STUDY OF SUPERIMPOSED FRACTURE MODES I, II AND III ON PMMA

A test apparatus has been developed to study the fracture behaviour of engineering materials subjected to superimposed tensile and shear (Mode I and II) loads using a single edge notch specimen. Stress intensity factors were calculated using finite element analysis. Test results for PMMA are reported. Results from circumferentially notched round bar specimens, subjected to combined tension and torsion (Mode I and III) loading are also reported. The Mode I/II results are consistent with the mixed mode fracture response of a wide range of brittle materials, although there is some evidence of non-linear behaviour. The fracture behaviour for superimposed Modes I and III indicates the strong influence of non-linear deformation which causes the mixed mode toughness to be dependent on the sequence and type of loading.     

A rapid dot-blot method for species identification of bloodstains

A very simple and rapid test for species identification is reported. Extracts of bloodstains were applied to a synthetic porous membrane and dried. The membrane was then quenched with glycine buffered saline containing BSA and Tween 20. A suspension of colloidal gold particles (GP) coated with rabbit antiserum to human IgG was poured onto, gently whirled and aspirated through the membrane. Spots from the human and monkey bloodstains became red, whereas those from other species of animals remained unstained. This test was completed within 3 to 4 min, and the antibody-coated GP reagent was prepared within 20 min using a very small quantity of antiserum. Cellulose acetate membranes of 0.45 microns or more in pore size were appropriate to this test.     

Assessing multidisciplinary areas of science and technology: A synthetic bibliometric study of Dutch nuclear energy research

This paper presents a selection of results of a comprehensive quantitative, research literature-based study of Dutch energy research. The primary goal of this paper is to provide an overview of what bibliometric data from ISI and non-ISI databases may offer to describe the state of affairs in a scientific field. It illustrates the added value of combining bibliometric indicators of publication output, international visibility, international co-operation, and interdisciplinarity in a study of nuclear energy research in the 1980's when its budget decreased dramatically.     

Chromosomal and genomic organization of Ty1-copia-like retrotransposon sequences in the genus Avena

Regulation of ligand-mediated signal transduction through transmembrane tyrosine kinase growth factor receptors involves phosphorylation of tyrosine residues in the intracellular domain of the receptor. The insulin-like growth factor-I (IGF-I) receptor contains three tyrosine residues in the carboxy-terminal domain at positions 1250, 1251, and 1316. Of these, only the tyrosine at position 1316 is conserved in the homologous position of the insulin receptor. Mutational analysis was used to study the role of these tyrosines in specific outcomes of IGF-I-mediated signal transduction. Mutations in the human IGF-I receptor were either replacement of tyrosines 1250 and 1251 with phenylalanine and histidine (yyFH), respectively, or replacement of the conserved distal tyrosine (position 1316) with phenylalanine (yCF). The yyFH mutation results in an IGF-I receptor with the amino acids found in the homologous position of the human insulin receptor. Cells overexpressing mutated IGF-I receptors were compared with cells expressing only endogenous IGF-I receptors or overexpressing wild-type IGF-I receptors. The ability of yyFH mutant IGF-I receptors to autophosphorylate the beta-subunit or phosphorylate insulin receptor substrate-1 was not significantly different from wild-type type IGF-I receptors. However, one or both of the proximal tyrosine residues (positions 1250 and 1251) in the carboxy-terminus of the IGF-I receptor are essential for IGF-I-stimulation of mitogenic and tumorigenic pathways. IGF-I-induced mitogenesis, measured as thymidine incorporation and cellular proliferation, was abrogated in cells overexpressing mutant IGF-I receptors with replacement of the proximal double tyrosines (positions 1250 and 1251). Fibroblasts expressing this mutant IGF-I receptor formed fewer tumors than the negative control cells, whereas cells expressing wild-type IGF-I receptors formed large tumors in all recipient mice injected. Conversely, cells expressing mutant IGF-I receptors with only the conserved distal tyrosine (position 1316) replaced had slightly reduced IGF-I-stimulated beta-subunit autophosphorylation, thymidine incorporation, and cellular proliferation when compared with cells expressing wild-type receptors. Phosphorylation of insulin receptor substrate-1 by the yCF mutant receptors was not impaired. Despite the ability of these mutant receptors to stimulate mitogenic growth, fibroblasts expressing this mutant receptor were also incapable of forming tumors in recipient nude mice. The distal tyrosine (position 1316) of the IGF-I receptor is crucial for tumor formation but is not essential for IGF-I stimulated mitogenesis. Thus, the tyrosine moieties in the carboxy-terminus of the IGF-I receptor participate in the signal transduction pathways that affect the mitogenic and tumorigenic potentials of cells expressing mutant IGF-I receptors.     

Dynamic effects in hot-carrier degradation relevant for CMOS operation

We describe different dynamic degradation effects in n- and p-MOSFETs as they are clearly proven and generally accepted to date. It turns out that they are connected with time constants in the oxide and at the interface and that time constants related to the device operation are too short to be relevant in this context. The effects are detrapping of fixed charges, the slow movement of holes in the oxide, an enhanced-degradation effect caused by alternating voltage conditions, during dynamic stress, and a post-stress interface state formation effect in nitride passivated n-MOSFETs. Furthermore, we discuss the relevance of those effects, under different operation conditions, finding that the fast non-stationary effects are of little significance. Only the “slow” effects, with time constants of seconds and above, play a role in reliability issues of MOSFETs.